This is a request for continued support to analyze variable region gene structure in the human immune system. Rheumatoid factors, antibodies to external antigens, and antibodies to other self-reacting components will be studied at the molecular level in order to determine the dynamic range of the human VH repertoire in defined immune responses. Mechanistically, we will study V/J junctional diversity in the human kappa and lambda systems, and D-D and D1-D fusions in the human heavy chain complex. Most of these studies are ongoing and represent extensions of work initiated under the first three years of this project.